Dr. Narula is in his third year as a fellow in the Pediatric Pulmonary Division at Columbia. He is fully trained and board certified in Pediatrics and is completing clinical training in Pediatric Pulmonology. His research training during the fellowship was initially focused on epithelial cell physiology (transepithelial fluid movement) t Columbia and he is now beginning work on epithelial cell biology (surface distribution of proteins in polarized epithelial cells) in Dr. Rodriguez-Boulan's laboratory at Cornell. The goal of the research plan is to elucidate the nature of the signals involved in the targeting of proteins into different surface domains of epithelial cells and the mechanism by which these signals operate. the human EGF receptor, NGF receptor, and several mutants of each of these will be transfected into MDCK cells and their surface distribution will be studied by biotinylation and targeting assays developed in Dr. Rodriguez-Boulan's laboratory. Basolateral sorting receptors will be identified by in vitro assays with perforated/transfected cells and then isolated by crosslinking experiments. The skills developed from these studies will enable Dr. Narula to study trafficking and polarization of CFTR in polarized epithelial cell lines expressing CFTR constitutively or in cells transfected with normal and mutant CFTR cDNA. Dr. Rodriguez-Boulan's laboratory is recognized for excellent training of post doctoral fellows and pioneering research on membrane and epithelial cells biology. In parallel with the research, Dr. Narula will take advanced courses in cell and molecular biology. Clinical activity to maintain skills will be limited to 15% effort and will be carried out in the Pediatric Pulmonary Division at Columbia where Dr. Narula will have an appointment as an Assistant Professor. On completion of the award, Dr. Narula will continue his academic career as an independent investigator in this Division.